Delta 9-Tetrahydrocannabinol (delta 9-THC, the active principle of marijuana, a psychoactive drug of abuse) given i.v., reduced the turnover rate of acetylcholine in hippocampus without affecting the hippocampal acetylcholine content whereas large doses of Cannabidiol, a non-psychoactive analogue of delta 9-THC, faliled to change hippocampal turnover rate of acetylcholine. (-) delta 8-THC and nabilone which are psychoactive reduced the turnover rate of acetycholine in hippocampus while (plus) delta 8-THC which is almost devoid of psychoactive properties caused only a small reduction in the hippocampal acetylcholine turnover given in doses 20 times greater than those of (-) delta 8-THC. Muscimol, a GABA agonist injected intraseptally, reduced the turnover rate of acetylcholine in the hippocampus. Furthermore, the inhibition by delta 9-THC and muscimol on hippocampal turnover rate of acetylcholine could be reversed by bicuculline, a GABA antagonist, injected intraseptally. Finally, delta 9-THC given intravenously increased the turnover rate of GABA in septum. These results suggest that the presence of inhibitory GABAergic interneurons in septum are necessary for delta 9-THC to specifically reduce the hippocampal turnover rate of acetylcholine.